Contextualizing the Impact of Pop Culture on Breast Implant Illness and its Medical Relevance.

INTRODUCTION: Despite a lack of data demonstrating causation, there is growing concern over breast implants and systemic illness. This study examines the impact of rising public interest in breast implant illness (BII) and its implications on breast implant removals (BIR). METHODS: A Google Trends (GT) analysis of each year between 2010 and 2022 was performed globally, and then separately for the United States alone (US), using the search terms "capsular contracture," "breast implant illness," and "breast implant(s) removal". Linear regression was performed to determine significant correlations. Data on BII-related Facebook advocacy groups, relevant pop culture events, numbers of BIR surgeries, and number of BII-related publications were collected and analyzed alongside GT data to determine relevance. RESULTS: For global GT, there was a significant relationship between "breast implant illness" and "breast implant(s) removal" in 2016 (R2=0.62, ß =0.33, p<0.01), 2020 (R2=0.53, ß =0.23, p=0.01), and 2022 (R2=0.60, ß =0.44, p=0.01). In the US, 2016 (R2=0.53, ß =1.75, p=0.01) 2018 (R2=0.61, ß =1.93, p<0.01) and 2020 (R2=0.72, ß=0.91, p<0.01) were significant. In 2020, "capsular contracture" and "breast implant(s) removal" was significant in the US (R2=0.58, ß=0.4, p=0.01). In 2016, Facebook was the platform for the largest BII advocacy group and in 2020 YouTube was the platform for the first BII documentary and TEDx talk. From 2010 to 2020, PubMed publications containing "ASIA" and "BII" increased 24-fold and ASPS reports on BIR rose 70%. CONCLUSION: This study suggests that BII is a topic of global concern and has implications on both academic medicine and clinical practice. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Timosaponin BII inhibits TGF-ß mediated epithelial-mesenchymal transition through Smad-dependent pathway during pulmonary fibrosis.

Pulmonary fibrosis (PF) is a progressive and fatal interstitial lung disease with limited therapeutic options at present, and epithelial-mesenchymal transition (EMT) is recognized as a major cause of lung fibrosis. Our previous work has confirmed that total extract of Anemarrhena asphodeloides Bunge [Asparagaceae] exerted the effect of anti-PF. As a main constituent of Anemarrhena asphodeloides Bunge [Asparagaceae], the effect of timosaponin BII (TS BII) on drug-induced EMT process in PF animals and alveolar epithelial cells remains unknown. In this study, we evaluated the effect of TS BII on bleomycin (BLM)-induced PF. The results showed that TS BII could restore the structure of lung architecture and MMP-9/TIMP-1 balance in fibrotic rat lung and inhibit collagen deposition. Moreover, we found that TS BII could reverse the abnormal expression of TGF-ß1 and EMT-related marker proteins including E-cadherin, vimentin, and α-SMA. Besides, aberrant TGF-ß1 expression and phosphorylation of Smad2 and Smad3 in BLM-induced animal model and TGF-ß1-induced cell model were downregulated by TS BII treatment, indicating that EMT in fibrosis was suppressed by inhibition of TGF-ß/Smad pathway both in vivo and in vitro. In summary, our study suggested that TS BII could be a promising candidate for PF treatment.

Acute toxicity, 28-day repeated-dose toxicity and toxicokinetic study of timosaponin BII in beagle dogs.

The safety evaluation of timosaponin BII (TBII) in beagle dogs with toxicokinetic study was performed. For the acute oral toxicity study, the minimum lethal dose (MLD) of TBII was more than 2000 mg/kg and suggested the characteristics of absorption saturation. For the 28-day repeated dose oral toxicity and toxicokinetic studies, there was no significant effect on all test parameters except for prolonged APTT in the 60 and 180 mg/kg groups, which recovered after withdrawal. The increase of drug exposure of 180 mg/kg group was not proportional to the increase of administration dose, showing the characteristics of absorption saturation.

New Insights into Dose-Dependent Effects of Curcumin on ARPE-19 Cells.

Opposing dose-dependent effects of curcumin (Cur) have been documented in Retinal Pigment Epithelium (RPE); therefore, to shed the light on the mechanisms of action is crucial for ophthalmic applications. On this basis we explored new insights about the dose-dependent mechanisms triggered by Cur in human retinal pigment epithelial cells (ARPE-19). Three concentrations (0.01 mM; 0.05 mM; 0.1 mM) of Cur were tested, followed by morphological, molecular, and functional analysis of the cells. Cur 0.01 mM promotes a significant increase in cell proliferation, not affecting cell cycle progression and apoptosis; by contrast, Cur 0.05 mM and 0.1 mM block cellular proliferation and trigger S-phase cell cycle arrest without inducing apoptosis. The observation of neuronal-like morphological changes in Cur 0.05 mM and 0.1 mM were not associated with neuronal differentiation, as observed by the quantification of Neurofilament-200 and by the analysis of voltage-dependent currents by patch clamp. Evaluation of autophagic markers LC3BII and p62 revealed significant modulations, suggesting an important activation of autophagy in ARPE-19 cells treated with Cur 0.05 mM and Cur 0.1 mM; conversely, Cur 0.01 mM did not affect autophagy. Altogether, our findings show new dose-dependent mechanisms of action of Cur that suggest a wide therapeutic application in ocular diseases with different pathogenesis (i.e., proliferative vitreoretinopathy or Age-Related Macular Degeneration).

Class B Scavenger Receptors BI and BII Protect against LPS-Induced Acute Lung Injury in Mice by Mediating LPS.

Recent studies suggest an anti-inflammatory protective role for class B scavenger receptor BI (SR-BI) in endotoxin-induced inflammation and sepsis. Other data, including ours, provide evidence for an alternative role of SR-BI, facilitating bacterial and endotoxin uptake and contributing to inflammation and bacterial infection. Enhanced endotoxin susceptibility of SR-BI-deficient mice due to their anti-inflammatory glucocorticoid deficiency complicates the understanding of SR-BI's role in endotoxemia/sepsis, calling for the use of alternative models. In this study, using human SR-BI (hSR-BI) and hSR-BII transgenic mice, we found that SR-BI and, to a lesser extent, its splicing variant SR-BII protect against LPS-induced lung damage. At 20 h after intratracheal LPS instillation, the extent of pulmonary inflammation and vascular leakage was significantly lower in hSR-BI and hSR-BII transgenic mice than in wild-type mice. Higher bronchoalveolar lavage fluid (BALF) inflammatory cell count and protein content and lung tissue neutrophil infiltration found in wild-type mice were associated with markedly (2 to 3 times) increased proinflammatory cytokine production compared to these parameters in transgenic mice following LPS administration. The markedly lower endotoxin levels detected in BALF of transgenic versus wild-type mice and the significantly increased BODIPY-LPS uptake observed in lungs of hSR-BI and hSR-BII mice 20 h after the i.t. LPS injection suggest that hSR-BI- and hSR-BII-mediated enhanced LPS clearance in the airways could represent the mechanism of their protective role against LPS-induced acute lung injury.

Biotransformation of Timosaponin BII into Seven Characteristic Metabolites by the Gut Microbiota.

Timosaponin BII is one of the most abundant Anemarrhena saponins and is in a phase II clinical trial for the treatment of dementia. However, the pharmacological activity of timosaponin BII does not match its low bioavailability. In this study, we aimed to determine the effects of gut microbiota on timosaponin BII metabolism. We found that intestinal flora had a strong metabolic effect on timosaponin BII by HPLC-MS/MS. At the same time, seven potential metabolites (M1-M7) produced by rat intestinal flora were identified using HPLC/MS-Q-TOF. Among them, three structures identified are reported in gut microbiota for the first time. A comparison of rat liver homogenate and a rat liver microsome incubation system revealed that the metabolic behavior of timosaponin BII was unique to the gut microbiota system. Finally, a quantitative method for the three representative metabolites was established by HPLC-MS/MS, and the temporal relationship among the metabolites was initially clarified. In summary, it is suggested that the metabolic characteristics of gut microbiota may be an important indicator of the pharmacological activity of timosaponin BII, which can be applied to guide its application and clinical use in the future.

A dynamic view of DNA structure within the nucleosome: Biological implications.

Most of eukaryotic cellular DNA is packed in nucleosome core particles (NCPs), in which the DNA (DNANCP) is wrapped around histones. The influence of this organization on the intrinsic local dynamics of DNA is largely unknown, in particular because capturing such information from experiments remains notoriously challenging. Given the importance of dynamical properties in DNA functions, we addressed this issue using CHARMM36 MD simulations of a nucleosome containing the NCP positioning 601 sequence and four related free dodecamers. Comparison between DNANCP and free DNA reveals a limited impact of the dense DNA-histone interface on correlated motions of dinucleotide constituents and on fluctuations of inter base pair parameters. A characteristic feature intimately associated with the DNANCP super-helical path is a set of structural periodicities that includes a marked alternation of regions enriched in backbone BI and BII conformers. This observation led to uncover a convincing correspondence between the sequence effect on BI/BII propensities in both DNANCP and free DNA, strengthening the idea that the histone preference for particular DNA sequences relies on those intrinsic structural properties. These results offer for the first time a detailed view of the DNA dynamical behavior within NCP. They show in particular that the DNANCP dynamics is substantial enough to preserve the ability to structurally adjust to external proteins, for instance remodelers. Also, fresh structural arguments highlight the relevance of relationships between DNA sequence and structural properties for NCP formation. Overall, our work offers a more rational framework to approach the functional, biological roles of NCP.

Interplay between oxidative stress and autophagy function and its role in inflammatory cytokine expression induced by palmitate in skeletal muscle cells.

Autophagy is a cellular process activated in response to various stresses such as starvation, hypoxia, and oxidative stress. Autophagy was reported to modulate the inflammatory pathways. However, whether autophagy is involved in regulation of palmitate-induced inflammation of skeletal muscle C2C12 cells is still unknown. The present study aimed to investigate the autophagic pathway in C2C12 cells treated with 0.5 mM palmitate. The results showed that the protein levels of LC3BII and P62 were increased in C2C12 cells after 12 h palmitate treatment. Besides, inhibition of autophagy by chloroquine or 3-methyladenin and its activation by rapamycin were associated with elevated mRNA and protein levels of IL-6 and TNF-α inflammatory cytokines in C2C12 cells. To study the mechanism by which autophagy impairment leads to activation of inflammatory responses, reactive oxygen species (ROS) levels in palmitate-treated cells were measured. The results showed that while palmitate stimulates ROS production, pretreatment of the cells with N-acetyl cysteine (NAC), a ROS scavenger, reduced inflammatory responses and also improved LC3-BII and P62 protein in the C2C12 cells exposed to palmitate. These findings suggest that palmitate-induced defect of autophagic flux leads to elevated inflammatory cytokine expression in the skeletal muscle cells by regulating the oxidative stress process.

Lipidomics Analysis of Timosaponin BII in INS-1 Cells Induced by Glycolipid Toxicity and Its Relationship with Inflammation.

Anemarrhena asphodeloides Bunge is a traditional Chinese medicine. The timosaponin BII is one of the most abundant and widely studied active ingredients in Anemarrhena asphodeloides Bunge. Related studies have shown that timosaponin BII has potential value for development and further utilization. The protective effect of timosaponin BII on islet ß cells under type 2 diabetes was investigated in the glycolipid toxic INS-1 cell model and possible biomarkers were explored by lipidomics analysis. Timosaponin BII was isolated from Anemarrhena asphodeloides Bunge by polyamide resin and Sephadex LH-20. Then, the glycolipid toxicity INS-1 cell model was established to investigate the protective effect of timosaponin BII. The results showed that timosaponin BII could significantly influence the levels of malondialdehyde (MDA) and glutathione (GSH), thereby restoring the insulin secretion ability and cell viability of model cells. Lipidomics analysis was combined with multivariate statistical analysis for marker selection. The four most common pathological and pharmacological lipid markers were phosphatidylserine (PS), suggesting that timosaponin BII had protective effects on model cells related to the reduction oxidative stress and macrophage inflammation. RAW264.7 macrophages were stimulated by LPS to establish a model of inflammation and study the effect of timosaponin BII on the nodes of NOD-like receptor P3 (NLRP3) inflammasome pathway in the model cells. In conclusion, timosaponin BII may have the effect of protecting INS-1 pancreatic ß cells through reducing IL-1ß (interleukin-1ß) production by inhibiting the NLRP3 inflammasome in macrophage and restoring the insulin secretion ability and cell viability by reducing oxidative stress.

Protective effects of timosaponin BII on oxidative stress damage in PC12 cells based on metabolomics.

Peroxide and oxygen free radicals are some of the causes of oxidative stress in brain tissue, and could lead to the change of brain structure and function. In addition, oxidative damage is one of the most important causes of the aging of the vast majority of tissues. The aim of this study is to investigate the protective effect of timosaponin BII on oxidative stress damage of PC12 induced by H2 O2 using metabolomics based on the UHPLC-Q-TOF-MS technique. Partial least-squares discriminant analysis method was used to identify 35 metabolites as decisive marker compounds in a preliminary interpretation of the mechanism of the antioxidative effect of timosaponin BII. The majority of these metabolites are involved in the glutathione metabolism, amino acid metabolism, sphingolipid and glycerophospholipid metabolism. Our results suggest that timosaponin BII demonstrates systematic antioxidant effects in the PC12 oxidative damage cell model via the regulation of multiple metabolic pathways. These findings provide insight into the pathophysiological mechanisms underlying oxidative stress damage and suggest innovative and effective treatments for this disorder, providing a reliable basis for the development of novel therapeutic target in timosaponin BII treatment of oxidative stress.

A gender invariant model of disgust propensity in blood-injection-injury phobia in Latina/o individuals.

Latinas/os have been underrepresented in research investigating the role of disgust propensity in phobias. The current study was the first to examine associations between disgust propensity and Blood-Injection-Injury (BII) phobia, when acculturation was controlled for, in Latina/o Americans (n = 376). A structural model was developed with a BII fear latent variable consisting of fears of injection, blood, and sharp objects (causing injuries). The disgust propensity latent variable was formed with three domains of core, animal reminder, and contamination disgust elicitors. In the model, disgust propensity predicted BII fear when controlling for acculturation. A series of measurement and structural invariance tests demonstrated that the model was invariant between males and females. The current findings supported the hypothesis that disgust plays a role in BII fear symptoms similarly in Latinas and Latinos. The findings are expected to improve our understanding of mechanisms and treatment approaches for BII phobia symptoms in this underserved cultural group.

Synthesis of 2D Layered BiI3 Nanoplates, BiI3 /WSe2 van der Waals Heterostructures and Their Electronic, Optoelectronic Properties.

Two-dimensional layered materials (2DLMs) have attracted considerable recent interest as a new material platform for fundamental materials science and potential new technologies. Here we report the growth of layered metal halide materials and their optoelectronic properties. BiI3 nanoplates can be readily grown on SiO2 /Si substrates with a hexagonal geometry, with a thickness in the range of 10-120 nm and a lateral dimension of 3-10 µm. Transmission electron microscopy and electron diffraction studies demonstrate that the individual nanoplates are high quality single crystals. Micro-Raman studies show characteristic Ag band at ≈115 cm-1 with slight red-shift with decreasing thickness, and micro-photoluminescence studies show uniform emission around 690 nm with blue-shift with decreasing thickness. Electrical transport studies of individual nanoplates show n-type semiconductor characteristics with clear photoresponse. Further, the BiI3 can be readily grown on other 2DLMs (e.g., WSe2 ) to form van der Waals heterostructures. Electrical transport measurements of BiI3 /WSe2 vertical heterojunctions demonstrate p-n diode characteristics with gate-tunable rectification behavior and distinct photovoltaic effect. The synthesis of the BiI3 nanoplates can expand the library of 2DLMs and enable a wider range of van der Waals heterostructures.

4-Acetylantroquinonol B suppresses autophagic flux and improves cisplatin sensitivity in highly aggressive epithelial cancer through the PI3K/Akt/mTOR/p70S6K signaling pathway.

Targeting residual self-renewing, chemoresistant cancerous cells may represent the key to overcoming therapy resistance. The entry of these quiescent cells into an activated state is associated with high metabolic demand and autophagic flux. Therefore, modulating the autophagy pathway in aggressive carcinomas may be beneficial as a therapeutic modality. In this study, we evaluated the anti-tumor activities of 4-acetylantroquinonol B (4-AAQB) in chemoresistant ovarian cancer cells, particularly its ability to modulate autophagy through autophagy-related genes (Atg). Atg-5 was overexpressed in invasive ovarian cancer cell lines and tissue (OR: 5.133; P=0.027) and depleting Atg-5 in ES-2 cell lines significantly induced apoptosis. 4-AAQB effectively suppressed viability of various subtypes of ovarian cancer. Cells with higher cisplatin-resistance were more responsive to 4-AAQB. For the first time, we demonstrate that 4-AAQB significantly suppress Atg-5 and Atg-7 expression with decreased autophagic flux in ovarian cancer cells via inhibition of the PI3K/Akt/mTOR/p70S6K signaling pathway. Similar to Atg-5 silencing, 4-AAQB-induced autophagy inhibition significantly enhanced cell death in vitro. These results are comparable to those of hydroxychloroquine (HCQ). In addition, 4-AAQB/cisplatin synergistically induced apoptosis in ovarian cancer cells. In vivo, 4-AAQB/cisplatin also significantly induced apoptosis and autophagy in an ES-2 mouse xenografts model. This is the first report demonstrating the efficacy of 4-AAQB alone or in combination with cisplatin on the suppression of ovarian cancer via Atg-5-dependent autophagy. We believe these findings will be beneficial in the development of a novel anti-ovarian cancer therapeutic strategy.

Acute toxicity, 28-day repeated-dose toxicity and toxicokinetic study of timosaponin BII in rats.

Timosaponin BII (TBII), a major steroidal saponin isolated from Anemarrhena asphodeloides Bge., displays a variety of promising pharmacological activities, such as neuroprotection, enhancement of learning and memory, vascular protection and inhibition of platelet aggregation; therefore, it has been developed as a pharmaceutical for prevention or treatment of dementia. Given the safety concerns surrounding timosaponins and the absence of studies on the safety of TBII, the potential toxicity of TBII was evaluated in toxicity and toxicokinetic studies in rats. In the acute oral toxicity study, loose stools were observed in rats receiving 4000 mg/kg, and the symptoms recovered within 1 day. In the 28-day repeated-dose oral toxicity and toxicokinetic study, rats receiving 540 mg/kg showed loose stools and a slight deceleration of body weight growth in both sexes, and the females also showed a slight decrease in food consumption. Moreover, urinalysis indicated reversible treatment-related toxicity in rats receiving 540 mg/kg. The toxicokinetic study demonstrated a dose-dependent increase in systematic exposure to TBII after 28 successive days of oral treatment with TBII. The accumulation coefficients of TBII were 4.35, 1.70 and 1.81, respectively, in rats that received 60, 180 and 540 mg/kg. The no-observed-adverse-effect level (NOAEL) is proposed to be 180 mg/kg.

Identification of Novel Vacuolin-1 Analogues as Autophagy Inhibitors by Virtual Drug Screening and Chemical Synthesis.

Autophagy is a fundamental cellular degradation process which is essential for cell homeostasis, and dysfunctional autophagy has been associated with a variety of human diseases, such as cancer. Several autophagy chemical modulators have been applied in a number of preclinical or clinical trials against these autophagy related diseases, especially cancer. Small molecule vacuolin-1 potently and reversibly inhibits both endosomal-lysosomal trafficking and autophagosome-lysosome fusion, yet the molecular mechanisms underlying vacuolin-1 mediated autophagy inhibition remain unknown. Here, we first performed the virtual drug screening and identified 14 vacuolin-1 analogues as autophagy inhibitors. Based on these virtual screening results, we further designed and synthesized 17 vacuolin-1 analogues, and found that 13 of them are autophagy inhibitors and a couple of them are as potent as vacuolin-1. In summary, these studies expanded the pool of useful autophagy inhibitors and reveal the structural-activity relationship of vacuolin-1 analogues, which is useful for future development of vacuolin-1 analogues with high potency and for identification of the molecular targets of vacuolin-1.

Timosaponin B-II ameliorates scopolamine-induced cognition deficits by attenuating acetylcholinesterase activity and brain oxidative damage in mice.

Timosaponin B-II (TB-II) is a main active saponin isolated from the rhizome of Anemarrhena asphodeloides Bge., which is widely used in traditional Chinese medicine. In this study, the effect of TB-II on learning and memory was investigated in a scopolamine-induced mouse model of Alzheimer's disease. The results of behavioral tests indicated that TB-II significantly increased the spontaneous alternation in the Y-maze test, and reversed the shortening of step-through latency induced by scopolamine in the passive avoidance test, showing protective effects on short-term and working memory. In the Morris water maze test, TB-II reduced the escape latency time in the training trial, and increased the swimming time in the target quadrant in the probe trial. Biochemical data demonstrated that TB-II significantly inhibited acetylcholinesterase (AChE) activity in the cerebral cortex and hippocampus of mice. Moreover, TB-II markably attenuated the reduction in glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities, and decreased malondialdehyde (MDA) levels, which are key biomarkers of brain oxidative stress. These results indicated that TB-II offers protection against scopolamine-induced deficits in learning and memory, possibly by inhibiting AChE and preventing oxidative stress damage. The findings suggested that TB-II has a potential therapeutic effect on cognitive and behavioral impairment.

Liver growth factor induces testicular regeneration in EDS-treated rats and increases protein levels of class B scavenger receptors.

The aim of the present work was to determine the effects of liver growth factor (LGF) on the regeneration process of rat testes after chemical castration induced by ethane dimethanesulfonate (EDS) by analyzing some of the most relevant proteins involved in cholesterol metabolism, such as hormone sensitive lipase (HSL), 3ß-hydroxysteroid dehydrogenase (3ß-HSD), scavenger receptor SR-BI, and other components of the SR family that could contribute to the recovery of steroidogenesis and spermatogenesis in the testis. Sixty male rats were randomized to nontreated (controls) and LGF-treated, EDS-treated, and EDS + LGF-treated groups. Testes were obtained on days 10 (T1), 21 (T2), and 35 (T3) after EDS treatment, embedded in paraffin, and analyzed by immunohistochemistry and Western blot. LGF improved the recovery of the seminiferous epithelia, the appearance of the mature pattern of Leydig cell interstitial distribution, and the expression of mature SR-BI. Moreover, LGF treatment resulted in partial recovery of HSL expression in Leydig cells and spermatogonia. No changes in serum testosterone were observed in control or LGF-treated rats, but in EDS-castrated animals LGF treatment induced a progressive increase in serum testosterone levels and 3ß-HSD expression. Based on the pivotal role of SR-BI in the uptake of cholesteryl esters from HDL, it is suggested that the observed effects of LGF would facilitate the provision of cholesterol for sperm cell growth and Leydig cell recovery.

Timosaponin B-II inhibits lipopolysaccharide-induced acute lung toxicity via TLR/NF-κB pathway.

Timosaponin B-II (TB), a main bioactive compound in Anemarrhena asphodeloides Bunge, has various kinds of pharmacological activities, the present study aimed to investigate the protective role of TB on lipopolysaccharide (LPS)-induced acute lung injury (ALI). ALI was induced in mice by intratracheal instillation of LPS, and TB (20 and 60 mg/kg) was given orally 1 h prior to LPS administration. After 6 h, bronchoalveolar lavagefluid (BALF) and lung tissue were collected. TB decreased LPS-induced evident lung histopathological changes, lung wet-to-dry weight (W/D) ratio and lung myeloperoxidase (MPO) activity. In addition, TB inhibited inflammatory cells and cytokines including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) in BALF. Furthermore, we demonstrated that TB inhibited the Toll-like receptor-2 (TLR2), Toll-like receptor-4 (TLR4), myeloid differentiation primary response gene-88 (MyD88), nuclear factor-κB (NF-κB) p65 in LPS-induced ALI. These results showed that administration of TB prior to LPS improves ALI, possibly mediating ALI through suppressing TLR/NF-κB pathway activation.

A novel LC-MS/MS method for determination of tissue distribution and excretion of timosaponin B-II in rat biological matrices.

Timosaponin B-II (TB-II) is a natural bioactive steroid glycoside extracted from the Chinese medicinal herb Anemarrhena asphodeloides Bge. (Fam. Liliaceae). It has been demonstrated to have a good anti-inflammatory effect and a low bioavailability (1.1%). Clinical research has focused on developing it into a completely new medicine. In this study, a rapid and sensitive analytical method based on LC-MS/MS has been developed for the determination of TB-II in rat biological matrices (tissues, bile, urine and feces samples). The analytes and internal standard were isolated from 100 µL samples by solid-phase extraction and then separated using a DIKMA Inertsil ODS-3 column (5 µm, 2.1 × 150 mm) with an isocratic mobile phase consisting of acetonitrile-0.05% formic acid (35:65) at a flow rate of 0.25 mL/min. Calibration curves (1/χ(2) -weighted) offered satisfactory linearity (r(2) ≥ 0.990) within the test range. The accuracy, precision, recoveries and matrix effects were satisfactory in all the biological matrices examined. The assay was successfully applied to a tissue distribution and excretion study in rats. The preclinical data are useful for the design of clinical trials of TB-II.

Breast implant illness: A United Kingdom patient-centred approach.

INTRODUCTION: Silicone breast implants are widely prevalent. An increasing group of patients detail self-reported somatic and psychological symptoms that have been ascribed as breast implant illness (BII) and seek capsulectomy and implant removal. To guide consultations and shared decision making, more outcome data relating to this intervention are required. AIM: To present a multicentre study of patient-centred (n = 100) outcome data, following total capsulectomy with implant removal for BII. METHOD: A questionnaire survey was cross-referenced with medical records. Collected data included demographics, operation details, pre- and postoperative symptom scores, overall self-perceived percentage improvement in BII symptoms and breast shape satisfaction ratings after explantation. RESULTS: The 10 most frequently self-reported symptoms were fatigue (81%), pains/aches (72%), brain/memory fog (56%), mood disturbances (36%), neuropathic pain (28%), hair loss (28%), headaches (25%), gastric symptoms/intolerances (24%), eczema/rash (18%) and vision disturbance (17%). A high proportion of patients (98%) experienced a 62 ±â€¯4% average symptom improvement; most self-reported symptoms (21/28) improved significantly after explantation with total capsulectomy (p < 0.05). Furthermore, patients had high overall self-perceived BII percentage improvement (76 ±â€¯3%) and satisfaction with breast shape numerical rating score (8 ±â€¯0.30) postoperatively. CONCLUSION: Despite BII not being a defined disease entity, symptom association with silicone breast implants continues for a growing number of patients. It is important to recognise that in this patient group, capsulectomy and implant removal may not be curative, however we have demonstrated that symptom improvement can occur. It is very difficult to prove a causal link between breast implants and BII; to do so will require extensive prospective data collection.